Alcohol use contributes to morbidity and mortality associated with HIV in numerous ways including (a) reducing antiretroviral medication adherence and efficacy, (b) contributing to worse virologic outcomes and immune functioning, (c) exacerbating liver dysfunction and hepatitis co-infection, and (d) exacerbating neurocognitive deficits associated with HIV. In addition, alcohol use among both HIV-infected and uninfected individuals is implicated in high-risk sexual behavior that leads to HIV transmission. Given multiple pathways through which alcohol impacts HIV morbidity, mortality and transmission, we propose an integrated, multifaceted, interdisciplinary approach to forward science on alcohol/HIV interactions and inform clinical approaches to caring for people living with HIV and efforts to prevent HIV transmission, both nationally and internationally. The overall aim of this Comprehensive Alcohol Research Center (CARC) is to conduct and disseminate multidisciplinary state-of-the-art research on biobehavioral interactions between alcohol and HIV and on interventions to reduce alcohol use among HIV-infected patients and individuals at high risk for HIV transmission. The CARC has 9 integrated parts: an Administrative Core , four Research Components, two Scientific Cores (Virology and Biostatistics), a Pilot Projects Component, and an Education/Dissemination Component that serves as a national resource for training and dissemination. Research activities address overlapping hypotheses regarding key variables (alcohol use, virology, hepatic function, neurocognitive function, use of antiretroviral therapy, and high-risk sexual behavior) and interrelationships among these variables using diverse methodologies (both animal and human research) and populations. These activities provide an integrated body of innovative alcohol/HIV research that can yield far greater total public health impact than any or all of them could if conducted independently. Further, this CARC will serve as the nexus for integration of alcohol/HIV science across proposed components, innovative pilot projects, complementary studies, and with other NIAAA Centers, yielding new insights into interactions between alcohol and HIV and into interventions to reduce drinking among those with HIV and others at risk for transmission.